title: Superficially projecting principal neurons in layer V of medial entorhinal cortex in the rat receive excitatory retrosplenial input.
abstract: Principal cells in layer V of the medial entorhinal cortex (MEC) have a nodal position in the cortical-hippocampal network. They are the main recipients of hippocampal output and receive inputs from several cortical areas, including a prominent one from the retrosplenial cortex (RSC), likely targeting basal dendrites of layer V neurons. The latter project to extrahippocampal structures but also relay information to the superficial layers of MEC, closing the hippocampal-entorhinal loop. In the rat, we electrophysiologically and morphologically characterized RSC input into MEC and conclude that RSC provides an excitatory input to layer V pyramidal cells. Ultrastructural analyses of anterogradely labeled RSC projections showed that RSC axons in layer V of MEC form predominantly asymmetrical, likely excitatory, synapses on dendritic spines (90%) or shafts (8%), with 2% symmetrical, likely inhibitory, synapses on shafts and spines. The overall excitatory nature of the RSC input was confirmed by an optogenetic approach. Patterned laser stimulation of channelrhodopsin-expressing presynaptic RSC axons evoked exclusively EPSPs in recorded postsynaptic layer V cells. All responding layer V pyramidal cells had an axon extending toward the white matter. Half of these neurons also sent an axon to superficial layers. Confocal imaging of RSC synapses onto MEC layer V neurons shown to project superficially by way of retrogradely labeling from superficial layers confirmed that proximal dendrites of superficially projecting cells are among the targets of inputs from RSC. The excitatory RSC input thus interacts with both entorhinal-cortical and entorhinal-hippocampal circuits.
authors.affiliation: Kavli Institute for Systems Neuroscience, Centre for Neural Computation, Faculty of Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway, and Neurobiology Center, Nencki Institute of Experimental Biology, 02-093 Warsaw, Poland.
authors.forename: Rafał
authors.initials: R
authors.lastname: Czajkowski
authors.forename: Jørgen
authors.initials: J
authors.lastname: Sugar
authors.forename: Sheng-Jia
authors.initials: SJ
authors.lastname: Zhang
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Couey
authors.forename: Jing
authors.initials: J
authors.lastname: Ye
authors.forename: Menno P
authors.initials: MP
authors.lastname: Witter
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure; D003712:Dendrites / Q000502:physiology / Q000648:ultrastructure; D018728:Entorhinal Cortex / Q000502:physiology* / Q000648:ultrastructure; D005260:Female; D006179:Gyrus Cinguli / Q000502:physiology* / Q000648:ultrastructure; D006624:Hippocampus / Q000502:physiology / Q000648:ultrastructure; D009434:Neural Pathways / Q000502:physiology / Q000648:ultrastructure; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000502:physiology*